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Rab30 facilitates lipid homeostasis during fasting

Author

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  • Danielle M. Smith

    (The Johns Hopkins University School of Medicine
    The Johns Hopkins University School of Medicine)

  • Brian Y. Liu

    (The Johns Hopkins University School of Medicine)

  • Michael J. Wolfgang

    (The Johns Hopkins University School of Medicine
    The Johns Hopkins University School of Medicine
    The Johns Hopkins University School of Medicine)

Abstract

To facilitate inter-tissue communication and the exchange of proteins, lipoproteins, and metabolites with the circulation, hepatocytes have an intricate and efficient intracellular trafficking system regulated by small Rab GTPases. Here, we show that Rab30 is induced in the mouse liver by fasting, which is amplified in liver-specific carnitine palmitoyltransferase 2 knockout mice (Cpt2L−/−) lacking the ability to oxidize fatty acids, in a Pparα-dependent manner. Live-cell super-resolution imaging and in vivo proximity labeling demonstrates that Rab30-marked vesicles are highly dynamic and interact with proteins throughout the secretory pathway. Rab30 whole-body, liver-specific, and Rab30; Cpt2 liver-specific double knockout (DKO) mice are viable with intact Golgi ultrastructure, although Rab30 deficiency in DKO mice suppresses the serum dyslipidemia observed in Cpt2L−/− mice. Corresponding with decreased serum triglyceride and cholesterol levels, DKO mice exhibit decreased circulating but not hepatic ApoA4 protein, indicative of a trafficking defect. Together, these data suggest a role for Rab30 in the selective sorting of lipoproteins to influence hepatocyte and circulating triglyceride levels, particularly during times of excessive lipid burden.

Suggested Citation

  • Danielle M. Smith & Brian Y. Liu & Michael J. Wolfgang, 2024. "Rab30 facilitates lipid homeostasis during fasting," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48959-x
    DOI: 10.1038/s41467-024-48959-x
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    1. Jiyoon Kim & Hyeyon Kim & Shin Hye Noh & Dong Geon Jang & Shi-Young Park & Dongkook Min & Hyunki Kim & Hee-Seok Kweon & Hoguen Kim & Sowon Aum & Sookyung Seo & Cheol Soo Choi & Hail Kim & Jae Woo Kim , 2020. "Grasp55−/− mice display impaired fat absorption and resistance to high-fat diet-induced obesity," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    2. Jae Man Lee & Martin Wagner & Rui Xiao & Kang Ho Kim & Dan Feng & Mitchell A. Lazar & David D. Moore, 2014. "Nutrient-sensing nuclear receptors coordinate autophagy," Nature, Nature, vol. 516(7529), pages 112-115, December.
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